rs763428520
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The ENST00000215095.11(STX1B):āc.845T>Cā(p.Ile282Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I282N) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000215095.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
STX1B | NM_052874.5 | c.845T>C | p.Ile282Thr | missense_variant | 10/10 | ENST00000215095.11 | NP_443106.1 | |
STX1B | XM_017022893.2 | c.827T>C | p.Ile276Thr | missense_variant | 10/10 | XP_016878382.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
STX1B | ENST00000215095.11 | c.845T>C | p.Ile282Thr | missense_variant | 10/10 | 1 | NM_052874.5 | ENSP00000215095 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152032Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249946Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135348
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461350Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 726976
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 152032Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
Generalized epilepsy with febrile seizures plus, type 9 Pathogenic:1Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Oct 30, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | research | Pediatrics, MediClubGeorgia | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Aug 24, 2022 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2024 | Apparently de novo variant in a patient with developmental and epileptic encephalopathy in published literature (PMID: 30737342); Observed in an individual referred for genetic testing at GeneDx who also had a different genetic etiology for the phenotype; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 35350397, 37066095, 35982159, 33057194, 30737342) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genetics Laboratory, Skane University Hospital Lund | May 27, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2022 | The c.845T>C (p.I282T) alteration is located in coding exon 10 of the STX1B gene. This alteration results from a T to C substitution at nucleotide position 845, causing the isoleucine (I) at amino acid position 282 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
STX1B-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 26, 2024 | The STX1B c.845T>C variant is predicted to result in the amino acid substitution p.Ile282Thr. This variant was reported de novo in an individual with STX1B-related disease (Wolking et al. 2019. PubMed ID: 30737342). This variant is reported in 0.0027% of alleles in individuals of European (Non-Finnish) descent in gnomAD, and It has conflicting interpretations in ClinVar, including likely benign and uncertain significance. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at